Blood pressure modulation in a cardiac care environment such as in a hypertensive emergency or during a cardiac perioperative procedure mainly relies on pharmacological approaches. With significant improvements and availabilities in antihypertensive drugs, uncontrolled blood pressure (BP) can be rapidly modulated within minutes. However, appropriate dosing of these drugs is characterized by high variability in patient response and a narrow acceptable range. Additionally, it is very difficult to reverse the antihypertensive effect of drugs in the case of drug-induced hypotension and when patients suffer from unwanted side effects; thus, pharmaceuticals are administered under strict control with the supervision of a skilled practitioner. Seeking new approaches to reduce the complications of the pharmacological solution, recent studies focusing on nerve stimulation have generated widespread interest in investigating and refining nerve stimulation strategies as an alternative therapy for controlling BP. In our ongoing investigation, we have demonstrated that electrical stimulation of a single ventral fascicle of the common peroneal nerve (vCPN) can significantly reduce the BP of hypertensive rats without significantly effecting heart rate and respiration. We further notice that stimulation parameters such as intensity, number of pulses, and frequency significantly influence the magnitude of the BP reduction. Based on our promising initial results, the objective of this research is to investigate the effect of nerve stimulation parameters on BP in order to develop a closed-loop control system. Using our implantable/removable Flexible polymer microchannel electrode array (FlexCEA), we plan to achieve sustainable BP reduction via electrical stimulation at the Sciatic nerve or its branch (CPN or vCPN). Towards this goal, we have two aims: Aim 1. Establish nerve stimulation parameters for reliably modulating BP using an animal model of hypertension. A quantitative relationship between the following stimulation parameters and BP will be established: frequency, pulse width, intensity, and various stimulation configurations. This data will provide for us the design parameters necessary for a closed-loop BP control system leading to new therapeutic modalities for hypertension control; Aim 2. Develop an adaptive closed-loop control system with real-time BP monitoring and neural stimulation to accurately modulate BP. Using Aim 1 data, a control system will be designed to apply a specified stimulation scheme to the target nerve through the FlexCEA for maintaining a reduced BP. Based on the success of a closed-loop application of neural stimulation to elicit sustainable BP reduction, this project may realize new strategies for hypertension control with the potential to avoid systemic side effects known in drug-based therapies.